Patients With Moderate Head Injury

Compagnone, Christian; D’Avella, Domenico; Servadei, Franco; Angileri, Filippo Flavio; Brambilla, G.; Conti, C; Cristofori, L.; Delfini, Roberto; Denaro, Luca; Ducati, Alessandro; Gaini, S. M.; Stefini, Roberto; Tomei, G.; Tagliaferri, Fernanda; Trincia, G; Tomasello, Francesco

doi:10.1227/01.neu.0000340796.18738.f7

Cited by 64 publications

(19 citation statements)

References 35 publications

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“…The percentage of patients with moderate TBI treated in ICUs in our study was high compared to other studies with moderate TBI patients. However, there are only a few comparable contemporary studies [ 3 , 4 , 7 , 8 ], and to our knowledge none has presented a cohort of moderate TBI patients from a single level 1 trauma centre. In our study, 27 % were mechanically ventilated on admission, as many as 84 % were admitted to an ICU and half of them stayed there three days or more.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, implementation of guidelines [ 17 , 18 ] for observation and treatment in intensive care units (ICUs) to avoid secondary brain injury have improved outcome in patients with severe TBI during the last decades [ 17 , 19 ]. On the other hand, contemporary studies describing injury severity and the acute phase in moderate TBI are scarce [ 3 , 4 , 7 , 8 ], which makes it difficult to evaluate and improve acute phase management for this patient group [ 1 ]. Also, results in studies of patients with moderate TBI are often reported together with results of patients with severe TBI, making precise judgments about this particular group difficult [ 6 – 8 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Moderate traumatic brain injury, acute phase course and deviations in physiological variables: an observational study

Lund

Gjeilo

Moen

et al. 2016

Scand J Trauma Resusc Emerg Med

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BackgroundPatients with moderate traumatic brain injury (TBI) are a heterogeneous group with great variability in clinical course. Guidelines for monitoring and level of care in the acute phase are lacking. The main aim of this observational study was to describe injury severity and the acute phase course during the first three days post-injury in a cohort of patients with moderate TBI. Deviations from defined parameters in selected physiological variables were also studied, based on guidelines for severe TBI during the same period.MethodsDuring a 5-year period (2004–2009), 119 patients ≥16 years (median age 47 years, range 16–92) with moderate TBI according to the Head Injury Severity Scale were admitted to a Norwegian level 1 trauma centre. Injury-related and acute phase data were collected prospectively. Deviations in six physiological variables were collected retrospectively.ResultsEighty-six percent of the patients had intracranial pathology on CT scan and 61 % had extracranial injuries. Eighty-four percent of all patients were admitted to intensive care units (ICUs) the first day, and 51 % stayed in ICUs ≥3 days. Patients staying in ICUs ≥3 days had lower median Glasgow Coma Scale score; 12 (range 9–15) versus 13 (range 9–15, P = 0.003) and more often extracranial injuries (77 % versus 42 %, P = 0.001) than patients staying in ICU 0–2 days. Most patients staying in ICUs ≥3 days had at least one episode of hypotension (53 %), hypoxia (57 %), hyperthermia (59 %), anaemia (56 %) and hyperglycaemia (65 %), and the proportion of anaemia related to number of measurements was high (33 %).ConclusionMost of the moderate TBI patients stayed in an ICU the first day, and half of them stayed in ICUs ≥3 days due to not only intracranial, but also extracranial injuries. Deviations in physiological variables were often seen in this latter group of patients. Lack of guidelines for patients with moderate TBI may leave these deviations uncorrected. We propose that in future research of moderate TBI, patients might be differentiated with regard to their need for monitoring and level of care the first few days post-injury. This could contribute to improvement of acute phase management.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Moderate traumatic brain injury, acute phase course and deviations in physiological variables: an observational study

Lund

Gjeilo

Moen

et al. 2016

Scand J Trauma Resusc Emerg Med

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“…This involves cascades of biological processes initiated at the time of injury that may persist over later days, weeks and perhaps, months, resultant to neuroinflammation, glutamate toxicity, ischemia, oxidative stress, astrocyte reactivity, blood-brain barrier changes, cellular dysfunction and apoptosis (Diaz-Arrastia et al, 2014; Greig et al, 2014). Previous studies found that hippocampal-associated learning and memory impairment were particularly vulnerable to secondary injury following TBI (Ariza et al, 2006; Compagnone et al, 2009; Hicks et al, 1993). A diverse array of animal TBI models, including controlled cortical impact (CCI) injury (Anderson et al, 2005; Hall et al, 2005; Myer et al, 2006), lateral fluid percussion (LFP) (Lowenstein et al, 1992; Thompson et al, 2005) and weight drop-induced closed diffuse injury (Golarai et al, 2001; Isaksson et al, 2001; Rachmany et al, 2013), have shown that TBI induces neuronal apoptosis in hippocampus.…”

Section: Introductionmentioning

confidence: 96%

Post-traumatic administration of the p53 inactivator pifithrin-α oxygen analogue reduces hippocampal neuronal loss and improves cognitive deficits after experimental traumatic brain injury

Yang

Greig

Huang

et al. 2016

Neurobiology of Disease

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Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Neuronal apoptosis in the hippocampus has been detected after TBI. The hippocampal dysfunction may result in cognitive deficits in learning, memory, and spatial information processing. Our previous studies demonstrated that a p53 inhibitor, pifithrin-α oxygen analogue (PFT-α (O)), significantly reduced cortical cell death, which is substantial following controlled cortical impact (CCI) TBI, and improved neurological functional outcomes via anti-apoptotic mechanisms. In the present study, we examined the effect of PFT-α (O) on CCI TBI-induced hippocampal cellular pathophysiology in light of this brain region’s role in memory. To investigate whether p53-dependent apoptosis plays a role in hippocampal neuronal loss and associated cognitive deficits and to define underlying mechanisms, SD rats were subjected to experimental CCI TBI followed by the administration of PFT-α or PFT-α (O) (2 mg/kg, i.v.) or vehicle at 5 h after TBI. Magnetic resonance imaging (MRI) scans were acquired at 24 h and 7 days post-injury to assess evolving structural hippocampal damage. Fluoro-Jade C was used to stain hippocampal sub-regions, including CA1 and dentate gyrus (DG), for cellular degeneration. Neurological functions, including motor and recognition memory, were assessed by behavioral tests at 7 days post injury. p53, p53 upregulated modulator of apoptosis (PUMA), 4-hydroxynonenal (4-HNE), cyclooxygenase-IV (COX IV), annexin V and NeuN were visualized by double immunofluorescence staining with cell-specific markers. Levels of mRNA encoding for caspase-3, p53, PUMA, Bcl-2, Bcl-2-associated X protein (BAX) and superoxide dismutase (SOD) were measured by RT-qPCR. Our results showed that post-injury administration of PFT-α and, particularly, PFT-α (O) at 5 h dramatically reduced injury volumes in the ipsilateral hippocampus, improved motor outcomes, and ameliorated cognitive deficits at 7 days after TBI, as evaluated by novel object recognition and open-field test. PFT-α and especially PFT-α (O) significantly reduced the number of FJC-positive cells in hippocampus CA1 and DG subregions, versus vehicle treatment, and significantly decreased caspase-3 and PUMA mRNA expression. PFT-α (O), but not PFT-α, treatment significantly lowered p53 and elevated SOD2 mRNA expression. Double immunofluorescence staining demonstrated that PFT-α (O) treatment decreased p53, annexin V and 4-HNE positive neurons in the hippocampal CA1 region. Furthermore, PUMA co-localization with the mitochondrial maker COX IV, and the upregulation of PUMA were inhibited by PFT-α (O) after TBI. Our data suggest that PFT-α and especially PFT-α (O) significantly reduce hippocampal neuronal degeneration, and ameliorate neurological and cognitive deficits in vivo via antiapoptotic and antioxidative properties.

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“…Hippocampal-associated learning and memory impairment is one of the most significant residual deficits following TBI, and is one of the most frequent patient symptoms (14–16). In part, because of a lack of understanding of the cellular and molecular mechanisms that lead to secondary cell death, there are currently no FDA-approved treatments available to prevent hippocampal cell death post-TBI.…”

Section: Introductionmentioning

confidence: 99%

Moderate Traumatic Brain Injury Triggers Rapid Necrotic Death of Immature Neurons in the Hippocampus

Zhou

Chen

Gao

et al. 2012

J Neuropathol Exp Neurol

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Traumatic brain injury (TBI) causes cell death predominantly in the cerebral cortex but there is additional secondary cell death in the hippocampus. We previously found that the majority of the dying cells in the mouse hippocampus are newborn immature granular neurons in a mouse model of lateral controlled cortical impact (CCI) injury with a moderate level of impact. It is not known how long this selective cell death in the hippocampal dentate gyrus lasts, and how it is induced. Using Fluoro-Jade B and immunohistochemistry, we show that most of the neuron death in the hippocampus occurs within 24 hours post-TBI and that cell death continues at low level for at least another 2 wks in this lateral CCI model. The majority of the dying immature granular neurons did not exhibit morphological characteristics of apoptosis and only a small subpopulation of the dying cells was positive for apoptotic markers. In contrast, most of the dying cells co-expressed the receptor-interacting protein-1, a marker of necrosis, suggesting that immature neurons mainly died of necrosis. These results indicate that moderate TBI mainly triggers rapid necrotic death of immature neurons in the hippocampus in a mouse CCI model.

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Patients With Moderate Head Injury

Cited by 64 publications

References 35 publications

Moderate traumatic brain injury, acute phase course and deviations in physiological variables: an observational study

Moderate traumatic brain injury, acute phase course and deviations in physiological variables: an observational study

Post-traumatic administration of the p53 inactivator pifithrin-α oxygen analogue reduces hippocampal neuronal loss and improves cognitive deficits after experimental traumatic brain injury

Moderate Traumatic Brain Injury Triggers Rapid Necrotic Death of Immature Neurons in the Hippocampus

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